Rania Habib, MD, DDS (Host): This is Transformational Pediatrics with Children's Mercy, Kansas City. I'm your host, Dr. Rania Habib. Today, we are having a panel discussion about the revised guidelines of Bactrim and acne. Bactrim is a commonly prescribed antibiotic used to treat a variety of conditions, including urinary tract infections, acne, skin, and soft tissue infections.

The American Academy of Dermatology recently revised its guidelines discouraging the use of Bactrim to treat acne based on research conducted by my next guests, Dr. Jenna Miller, a Pediatric Intensivist, and Dr. Jennifer Goldman, Infectious Disease Pediatrician at Children's Mercy, Kansas City. Welcome Dr. Goldman and Dr. Miller. We cannot wait to hear about this exciting research.

Jennifer Goldman, MD, MSCR: Hi, thanks for having us.

Jenna Miller, MD, FAAP: Yes, thank you for having us on today.

Rania Habib, MD, DDS (Host): In addition to the new acne guidelines, the FDA also revised its labeling of TPX SMX, more commonly known as Bactrim, a few years ago because of your research, which identified a rare but deadly side effect. You were the first to suspect a link between Bactrim and a severe respiratory illness back in 2018 while treating a patient whose story made national headlines.

Dr. Miller, can you share more on how you started to put the puzzle pieces together to make that connection?

Jenna Miller, MD, FAAP: As you mentioned, the story started back in 2018, but I actually met this patient in 2017. In 2017, she was admitted around Halloween, and I met her on a Saturday, and she began her journey on ECMO, which is life support, or lung support, on Monday. She was the longest running ECMO patient in our institution. And because of that, her mom was avid social media utilizer, and so because of the stories she shared online, there was a story on CNN Health about how our patient walked and talked on ECMO.

Host: Okay.

Jenna Miller, MD, FAAP: This article caught the attention of other patients and their families who felt like their stories were similar to our patient. They shared their medical histories that often led to severe lung failure requiring ECMO, lung transplant, or sometimes even death after bactrim exposure.

Host: Wow.

Jenna Miller, MD, FAAP: With this, I became curious if there was a relationship between all these patient stories. And that's when I reached out to my friend and colleague, Dr. Goldman, who I knew specialized in bactrim research.

Host: Mm hmm.

Jenna Miller, MD, FAAP: Together, we reviewed the first five adolescents that were referred to us. And thought their stories were too similar and all ultimately led to serious lung failure to not continue to investigate.

So we published the findings on those five adolescents in 2019 in Pediatrics, and since then we've been working to define this illness. Most recently, our three part definition was published in 2023 in Critical Care Medicine. Over these past five years, all of our patients have interestingly, been referred to us based on media stories or podcasts such as this, social media sharing, word of mouth, and now most recently via our publications.

Host: That's fantastic. Now, can you go over that? I know you mentioned that three step kind of criteria. Could you identify what that was?

Jenna Miller, MD, FAAP: So the first part is the clinical characteristics, and so that's what we first started working on in 2019 because that's all we had was the observations of these patients and their clinical traits. Since then, we were able to identify a novel pathology finding, so what we see under the microscope for histopathology, and that is similar between the patients that we were able to get tissue on.

And the third part most recently is a genetic link in the HLA genome that our wonderful genomic center helped us identify and every patient that we tested, has that HLA marker as well. So those are the three parts, clinical, pathology, and genomics.

Host: That is incredible. Now, Dr. Miller, as part of your research, how many patients to date have you identified as having a life threatening illness because they are taking Bactrim?

Jenna Miller, MD, FAAP: We've had 72 total contacts. Of those, we've included 24. We've had 8 deaths and 8 patients who required transplant.

Host: That's pretty severe. Now, Dr. Goldman, Bactrim is a commonly prescribed antibiotic. So, by hearing these statistics, eight patients needed a transplant, eight patients actually died from the complications. Is it safe?

Jennifer Goldman, MD, MSCR: Yeah, I think that's a great question. So Bactrim has been approved by the FDA since the 1970s. It's prescribed millions of times each year. And it is safe in most people. For those of us, you know, who are clinicians and learned about antibiotics early, kind of in our careers, we all learned that Bactrim rarely is associated with life threatening reactions. And so we learned about bad skin reactions, like Stevens Johnson. We learned about liver injury. But these are one in a million type of reactions. And I think what Dr. Miller and I have uncovered is just a new, very rare, but very severe reaction to Bactrim.

So in most cases, people tolerate Bactrim very well, but we're trying to better understand if we can determine who is at risk.

Host: What should physicians know before prescribing this drug?

Jennifer Goldman, MD, MSCR: We want physicians to know just again like they learned Bactrim can rarely cause a skin reaction. If you prescribe that antibiotic and your patient calls you and says, hey, my eyes are red or I have a rash. Your first response would be stop that antibiotic and then we can investigate. We want physicians to know and clinicians to recognize that, hey, if someone has taken Bactrim and develops unexplained respiratory symptoms, they start to develop cough, difficulty breathing, we want a good history of what medications they're on and if Bactrim is one of them, stop it.

You know, in the cases that we saw, many of the patients sought medical care many times and Bactrim was continued because it wasn't even really on the radar of a possible cause of their respiratory symptoms.

Host: Right. I guess that is because it's so new, we never learned that in med school, so it would be something that none of us would really look out for. What should families know before taking it now?

Jennifer Goldman, MD, MSCR: Yeah, I think similarly, I think as clinicians who are prescribing this antibiotic, we need to give good guidance to families. And same thing, hey, you're taking this antibiotic and if you develop cough, you're having difficulty breathing, or you develop a rash or something like that, go ahead and stop that medicine and call your provider right away.

There are bad reactions that can happen very rarely due to this antibiotic, and we want to make sure that if you experience it, we stop the medicine right away.

Host: That's incredible, and it's great advice to remind our physicians, to think of this complication, to remind the families that could happen so that they're aware of that. Dr. Goldman, how has your research on Bactrim evolved over the years?

Jennifer Goldman, MD, MSCR: I've been interested in Bactrim for a long time because I am an infectious disease doc. We use this antibiotic. Again, it's a really important antibiotic for us to have but I have seen those rare cases of these severe reactions, the skin reactions, the liver reactions and so I had been studying the antibiotic for quite a while just to really understand the mechanisms of why this drug causes these reactions. That was much more kind of in a laboratory setting. And I think with the work that I've been doing with Dr. Miller, it has really linked the clinical aspects of this. So, I mean, we really started at Zay's bedside and started with other patients and have now kind of worked backwards to try to better understand why these reactions are happening.

Host: It sounds like it's been such a wonderful collaboration. So Dr. Miller, could you speak to the importance of collaboration when it comes to research?

Jenna Miller, MD, FAAP: I think the stars kind of aligned for this particular endeavor to make to where it has. And so, when I was thinking to myself, gosh, I should reach out to my friend Jen and see what thinks about this crazy idea that these couple of cases and Zay are related to Bactrim. But because of that curiosity and I think ease at which I could talk to Jen, we were able to publish those first five cases in 2019.

And that was really the first part of the journey to having people believe that this was an actual disease process, and to get but-in to continue that work. And so the more we were able to share about our concerns about Bactrim as a trigger for a severe respiratory failure, the more requests for patient evaluations we received.

And because of that interest, we connected with the pathologists at Massachusetts General due to those news reports about our patient. And this led to that development of the understanding that this pathology finding existed. And they had seen it a couple of times, but we didn't know that.

Because we were able to collaborate, we figured out, hey, we're seeing the same thing, and we were able to put those pieces together. And then with the addition of our genomic marker, so because we have a great genome center here, and we were able to easily collaborate with them, we were able to put together this genomic marker.

So, it's been five years, which sometimes people say, well, gosh, how come it takes so long? But honestly, in five years to have a clinical definition, a pathology finding, and a genomic marker is really, I think, remarkable, and it could not have happened without us collaborating with Massachusetts General and our Genomic Center and each other.

Host: Absolutely. It's fantastic. So, Dr. Goldman, what is next for your research?

Jennifer Goldman, MD, MSCR: Yeah, we would love to come up with a clinical predictor, right? I mean, that's our goal. We want to try to prevent this from happening again. And so as Dr. Miller mentioned, we do have a, we've identified an association between a specific HLA. All the patients that we have to date have that HLA. However, 20 percent of the general population also have the, that HLA.

So that alone is not going to be a good marker. It's, you can't have this reaction likely without it, but many, many people have this genetic marker and don't have this reaction. And so now we really kind of want to explore mechanism because if we can know what's triggering what we think is the immune system?

Why is the immune system responding? What is it in this kind of genetic marker that really puts a patient at risk? Then potentially, in an ideal world, we could screen someone for it pretty easily before they took the antibiotic.

Host: That would be amazing, because then we could have a good understanding of who might have this reaction. Thank you guys so much for joining me today. It's been wonderful to hear about this collaborative effort that you guys have with Mass General and Children's Mercy, Kansas City. So I'd like to begin with Dr. Miller, any last pearls of wisdom for our audience today?

Jenna Miller, MD, FAAP: I think we're all so busy and we see cases that are perplexing and curious almost every day in our practice, whether you're in a hospital or in a clinic setting. And if something really jumps out at you as, gosh, could I help define this? Could I help figure this out? Just to try to follow that, that gut instinct, I suppose, and use the resources you have.

And I think this particular case is an interesting place where social media has powers of good, actually. And so, to not be afraid of that, I suppose.

Host: I love that message. And Dr. Goldman, your turn, what would you like to share with our audience as a pearl of wisdom from this wonderful story?

Jennifer Goldman, MD, MSCR: Yeah, I think we could not have done this without the families and families have been a critical part of all of this work. They've been willing to share stories, sometimes heart wrenching, about their loved ones. They've been able, you know, willing to share medical records and blood samples.

And so this kind of feels like a collaborative journey with the people that have been touched by this bad. disease process as well and we welcome other clinicians or people that hear this to if they think they know of a case to reach out to us that we are always serving as kind of, we are learning as we go and we'd like to be able to share our experiences with others.

Host: Absolutely. I love that spirit of collaboration. Well, thank you so much for joining me Once again, that was Dr. Jennifer Goldman and Dr. Jenna Miller from Children's Mercy, Kansas City. To refer your patient or for more information, please visit childrensmercy.org to get connected with one of our providers.

I'm your host, Dr. Rania Habib, wishing you well. This has been Transformational Pediatrics with Children's Mercy, Kansas City. Please remember to subscribe, rate, and review this podcast and all other Children's Mercy podcasts.